Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis—A Systematic Review and Meta-Analysis

Bewersdorf, Jan Philipp; Sheth, Amar H.; Vetsa, Shaurey; Grimshaw, Alyssa; Giri, Smith; Podoltsev, Nikolai A.; Gowda, Lohith; Tamari, Roni; Tallman, Martin S.; Rampal, Raajit K.; Zeidan, Amer M.; Stahl, Maximilian

doi:10.1016/j.jtct.2021.05.016

Cited by 9 publications

(3 citation statements)

References 75 publications

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“…Allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment modality for MF yet is usually reserved for patients in the intermediate- and high-risk group because of the risks of treatment-related morbidity and mortality. Despite improvements in post-HCT outcomes in recent years, OS is still unsatisfactory (5 years OS = 50%-60%), 26 , 27 with relapse and graft-versus-host disease the main causes of death. 26 There are limited data on the prognostic value of JAK2 V617F mutation or associated chromosomal alterations in patients with MF undergoing HCT, and whether possible differences based on the disease subtypes exist.…”

Section: Introductionmentioning

confidence: 99%

“…Despite improvements in post-HCT outcomes in recent years, OS is still unsatisfactory (5 years OS = 50%-60%), 26 , 27 with relapse and graft-versus-host disease the main causes of death. 26 There are limited data on the prognostic value of JAK2 V617F mutation or associated chromosomal alterations in patients with MF undergoing HCT, and whether possible differences based on the disease subtypes exist. This is particularly important because results may guide clinical decisions related to the use of JAK inhibitors after HCT for patients with MF.…”

Section: Introductionmentioning

confidence: 99%

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JAK2 V617F mutation and associated chromosomal alterations in primary and secondary myelofibrosis and post-HCT outcomes

Rafati,

Brown,

Zhou

et al. 2023

Blood Advances

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JAK2 V617F is the most common driver mutation in primary or secondary myelofibrosis for which allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment. Knowledge of the prognostic utility of JAK2 alterations in the HCT setting is limited. We identified all patients with MF who received HCT between 2000 and 2016 and had a pre-HCT blood sample (N = 973) available at the Center of International Blood and Marrow Transplant Research biorepository. PacBio sequencing and single nucleotide polymorphism–array genotyping were used to identify JAK2V617F mutation and associated mosaic chromosomal alterations (mCAs), respectively. Cox proportional hazard models were used for HCT outcome analyses. Genomic testing was complete for 924 patients with MF (634 primary MF [PMF], 135 postpolycythemia vera [PPV-MF], and 155 postessential thrombocytopenia [PET-MF]). JAK2V617F affected 562 patients (57.6% of PMF, 97% of PPV-MF, and 42.6% of PET-MF). Almost all patients with mCAs involving the JAK2 region (97.9%) were JAK2V617-positive. In PMF, JAK2V617F mutation status, allele burden, or identified mCAs were not associated with disease progression/relapse, nonrelapse mortality (NRM), or overall survival. Almost all PPV-MF were JAK2V617F-positive (97%), with no association between HCT outcomes and mutation allele burden or mCAs. In PET-MF, JAK2V617F high mutation allele burden (≥60%) was associated with excess risk of NRM, restricted to transplants received in the era of JAK inhibitors (2013-2016; hazard ratio = 7.65; 95% confidence interval = 2.10-27.82; P = .002). However, allele burden was not associated with post-HCT disease progression/relapse or survival. Our findings support the concept that HCT can mitigate the known negative effect of JAK2V617F in patients with MF, particularly for PMF and PPV-MF.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

JAK2 V617F mutation and associated chromosomal alterations in primary and secondary myelofibrosis and post-HCT outcomes

Rafati,

Brown,

Zhou

et al. 2023

Blood Advances

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“…Myelofibrosis (MF) is a debilitating disease for which allogeneic hematopoietic cell transplantation (allo-HCT) is the only cure [1]. Currently, 50-60% of MF patients who undergo allo-HCT can be cured [2], but less than 10% of MF patients actually receive this procedure due to concerns about its significant mortality rate, mainly during the first year [3]. This represents a major challenge in selecting appropriate candidates and determining the optimal timing for allo-HCT, especially considering the chronic and highly heterogeneous clinical course of the disease.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation in patients with CALR-mutated myelofibrosis: a study of the Chronic Malignancies Working Party of EBMT

Hernández-Boluda,

Eikema,

Koster

et al. 2023

Bone Marrow Transplant

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Allogeneic hematopoietic cell transplantation (allo-HCT) is curative for myelofibrosis (MF) but assessing risk-benefit in individual patients is challenging. This complexity is amplified in CALR-mutated MF patients, as they live longer with conventional treatments compared to other molecular subtypes. We analyzed outcomes of 346 CALR-mutated MF patients who underwent allo-HCT in 123 EBMT centers between 2005 and 2019. After a median follow-up of 40 months, the estimated overall survival (OS) rates at 1, 3, and 5 years were 81%, 71%, and 63%, respectively. Patients receiving busulfan-containing regimens achieved a 5-year OS rate of 71%. Non-relapse mortality (NRM) at 1, 3, and 5 years was 16%, 22%, and 26%, respectively, while the incidence of relapse/progression was 11%, 15%, and 17%, respectively. Multivariate analysis showed that older age correlated with worse OS, while primary MF and HLA mismatched transplants had a near-to-significant trend to decreased OS. Comparative analysis between CALR-and JAK2mutated MF patients adjusting for confounding factors revealed better OS, lower NRM, lower relapse, and improved graft-versushost disease-free and relapse-free survival (GRFS) in CALR-mutated patients. These findings confirm the improved prognosis associated with CALR mutation in allo-HCT and support molecular profiling in prognostic scoring systems to predict OS after transplantation in MF.

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Allogeneic haematopoietic stem cell transplantation for myelofibrosis: prognostic indicators and the role of JAK2V617F measurable-residual disease monitoring by droplet-digital polymerase chain reaction

Yim

Lee

et al. 2023

Ann Hematol

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Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis—A Systematic Review and Meta-Analysis

Cited by 9 publications

References 75 publications

JAK2 V617F mutation and associated chromosomal alterations in primary and secondary myelofibrosis and post-HCT outcomes

JAK2 V617F mutation and associated chromosomal alterations in primary and secondary myelofibrosis and post-HCT outcomes

Allogeneic hematopoietic cell transplantation in patients with CALR-mutated myelofibrosis: a study of the Chronic Malignancies Working Party of EBMT

Allogeneic haematopoietic stem cell transplantation for myelofibrosis: prognostic indicators and the role of JAK2V617F measurable-residual disease monitoring by droplet-digital polymerase chain reaction

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